US6818771B1ExpiredUtility

Process for the production of a naphthyridine carboxylic acid derivative (methanesulfonate sesquihydrate)

49
Assignee: LG LIFE SCIENCES LTDPriority: Sep 18, 1998Filed: Sep 15, 1999Granted: Nov 16, 2004
Est. expirySep 18, 2018(expired)· nominal 20-yr term from priority
Inventors:Jerome Francis HayesTimothy Charles WalsgroveAndrew Wells
C07D 471/04
49
PatentIndex Score
6
Cited by
29
References
21
Claims

Abstract

A process for the production of a naphthyridine carboxylic acid derivative having antibacterial activity.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
       1. A process for the production of 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate which comprises: (a) forming a crystallization solution comprising 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid, methanesulfonic acid, and a solvent comprising at least one least one water miscible cosolvent and water, wherein the ratio of water miscible cosolvent:water is in the range of 2:1 to 1:2 v/v, 
       (b) reacting said carboxylic acid and methanesulfonic acid in the solvent, and  
       (c) isolating the resulting solid product which comprises 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate.  
     
     
       2. A process according to  claim 1  wherein the water miscible cosolvent is a C 1-4  alcohol. 
     
     
       3. A process according to  claim 2  wherein the water miscible cosolvent is isopropanol. 
     
     
       4. A process according to  claim 1  wherein the ratio of water miscible cosolvent:water is 2:1 v/v. 
     
     
       5. A process according to  claim 1  wherein the ratio of 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid:solvent is 1:100 w/v or more. 
     
     
       6. A process according  claim 1  which uses from 0.7 to 1.5 mole equivalents of methanesulfonic acid. 
     
     
       7. A process according to  claim 1  wherein the crystallization solution is seeded with 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate to aid crystallization. 
     
     
       8. A process according to  claim 7  wherein the solution is seeded whilst at a temperature of ≧25° C. 
     
     
       9. A process according to  claim 8  wherein the solution is seeded whilst at a temperature of about 30° C. 
     
     
       10. A process for the production of 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate which comprises: 
       (a) forming a crystallization solution comprising 7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid, methanesulfonic acid, and a solvent comprising at least one least one C 1-4  alcohol and water, wherein the ratio of C 1-4  alcohol:water is in the range of 2:1 to 1:2 v/v, the ratio of said carboxylic acid to said solvent is 1:100 w/v or more, and from 0.7 to 1.5 mole equivalents of the methanesulfonic acid is used,  
       (b) reacting said carboxylic acid and methanesulfonic acid in the solvent, and  
       (c) isolating the resulting solid product which comprises 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate.  
     
     
       11. A process according to  claim 10  wherein the C 1-4  alcohol is isopropanol. 
     
     
       12. A process according to  claim 10  wherein the ratio of C 1-4  alcohol:water is 2:1 v/v. 
     
     
       13. A process according to  claim 10  wherein the crystallization solution is seeded with 7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate sesquihydrate to aid crystallization. 
     
     
       14. A process according to  claim 13  wherein the solution is seeded whilst at a temperature of ≧25° C. 
     
     
       15. A process according to  claim 13  wherein the solution is seeded whilst at a temperature of about 30° C. 
     
     
       16. A process according to  claim 1  wherein the methanesulfonate sesquihydrate is crystallized out of solution by cooling. 
     
     
       17. A process according to  claim 1  wherein the resulting solid product is dried. 
     
     
       18. A process according to  claim 1  wherein the resulting solid product is dried at 50-55° C. under vacuum. 
     
     
       19. A process according to  claim 10  wherein the methanesulfonate sesquihydrate is crystallized out of solution by cooling. 
     
     
       20. A process according to  claim 10  wherein the resulting solid product is dried. 
     
     
       21. A process according to  claim 10  wherein the resulting solid product is dried at 50-55° C. under vacuum.

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